314
Views
18
CrossRef citations to date
0
Altmetric
Reviews

Flavonoids sensitize tumor cells to radiation: molecular mechanisms and relevance to cancer radiotherapy

&
Pages 360-369 | Received 17 Sep 2019, Accepted 01 Nov 2019, Published online: 02 Dec 2019

References

  • Abdelmoaty MA, Ibrahim MA, Ahmed NS, Abdelaziz MA. 2010. Confirmatory studies on the antioxidant and antidiabetic effect of quercetin in rats. Indian J Clin Biochem. 25(2):188–192.
  • Adams GE. 1977. Hypoxic cell sensitizers for radiotherapy. In: Becker FF, editor. Radiotherapy, surgery, and immunotherapy. Boston, MA: Springer US; p. 181–223.
  • Ahire V, Kumar A, Mishra KP, Kulkarni G. 2017. Ellagic acid enhances apoptotic sensitivity of breast cancer cells to γ-radiation. Nutr Cancer. 69(6):904–910.
  • Alcorn S, Walker AJ, Gandhi N, Narang A, Wild AT, Hales RK, Herman JM, Song DY, Deweese TL, Antonarakis ES. 2013. Molecularly targeted agents as radiosensitizers in cancer therapy–focus on prostate cancer. IJMS. 14(7):14800–14832.
  • Arena S, Rappa C, Del Frate E, Cenci S, Villani C. 2002. A natural alternative to menopausal hormone replacement therapy. Phytoestrogens. Miner Ginecol. 54(1):53–57.
  • Benkovic V, Knezevic AH, Dikic D, Lisicic D, Orsolic N, Basic I, Kosalec I, Kopjar N. 2008. Radioprotective effects of propolis and quercetin in gamma-irradiated mice evaluated by the alkaline comet assay. Phytomedicine. 15(10):851–858.
  • Bristow RG, Alexander B, Baumann M, Bratman SV, Brown JM, Camphausen K, Choyke P, Citrin D, Contessa JN, Dicker A, et al. 2018. Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology. Lancet Oncol. 19(5):e240–e251.
  • Brown JM, Carlson DJ, Brenner DJ. 2014. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 88(2):254–262.
  • Chahar MK, Sharma N, Dobhal MP, Joshi YC. 2011. Flavonoids: a versatile source of anticancer drugs. Phcog Rev. 5(9):1–12.
  • Chandarlapaty S. 2012. Negative feedback and adaptive resistance to the targeted therapy of cancer. Cancer Discov. 2(4):311–319.
  • Cheng NN, Starkewolf Z, Davidson RA, Sharmah A, Lee C, Lien J, Guo T. 2012. Chemical enhancement by nanomaterials under X-ray irradiation. J Am Chem Soc. 134(4):1950–1953.
  • Cho HJ, Ahn KC, Choi JY, Hwang SG, Kim WJ, Um HD, Park JK. 2015. Luteolin acts as a radiosensitizer in nonsmall cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade. Int J Oncol. 46(3):1149–1158.
  • Cho JJ, Chae JI, Yoon G, Kim KH, Cho JH, Cho SS, Cho YS, Shim JH. 2014. Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma. Int J Oncol. 45(2):667–674.
  • Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. 2010. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 15(4):360–371.
  • Comalada M, Camuesco D, Sierra S, Ballester I, Xaus J, Galvez J, Zarzuelo A. 2005. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur J Immunol. 35(2):584–592.
  • Davis TA, Mungunsukh O, Zins S, Day RM, Landauer MR. 2008. Genistein induces radioprotection by hematopoietic stem cell quiescence. Int J Radiat Biol. 84(9):713–726.
  • Dayal R, Singh A, Pandey A, Mishra K. 2014. Reactive oxygen species as mediator of tumor radiosensitivity. J Can Res Ther. 10(4):811–818.
  • Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. 2007. Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches. Indian J Pharmacol. 39(4):172–179.
  • Erdogan A, Most AK, Wienecke B, Fehsecke A, Leckband C, Voss R, Grebe MT, Tillmanns H, Schaefer CA, Kuhlmann CR. 2007. Apigenin-induced nitric oxide production involves calcium-activated potassium channels and is responsible for antiangiogenic effects. J Thromb Haemost. 5(8):1774–1781.
  • Falcone Ferreyra ML, Rius SP, Casati P. 2012. Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front Plant Sci. 3:222.
  • Fraschini F, Demartini G, Esposti D. 2002. Pharmacology of Silymarin. Clin Drug Investigat. 22(1):51–65.
  • Galati G, O'Brien PJ. 2004. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radical Biol Med. 37(3):287–303.
  • Garg AK, Buchholz TA, Aggarwal BB. 2005. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxidants Redox Signal. 7(11–12):1630–1647.
  • Gibellini L, Pinti M, Nasi M, Montagna JP, De Biasi S, Roat E, Bertoncelli L, Cooper EL, Cossarizza A. 2011. Quercetin and cancer chemoprevention. Evidence-Based Complement Alternat Med eCAM. 2011:591356.
  • Girdhani S, Bhosle S, Thulsidas S, Kumar A, Mishra K. 2005. Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Can Res Ther. 1(3):129–131.
  • Gong C, Yang Z, Zhang L, Wang Y, Gong W, Liu Y. 2017. Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway. OTT. 11:17–27.
  • Haddad Y, Vallerand D, Brault A, Haddad PS. 2011. Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis. Evidence-Based Complement Alternat Med eCAM. 2011:1.
  • Hall EJ. 2000. Radiobiology for the radiologist. 5th ed. Philadelphia (PA): Lippincott Williams & Wilkins.
  • Hardmeier R, Hoeger H, Fang-Kircher S, Khoschsorur A, Lubec G. 1997. Transcription and activity of antioxidant enzymes after ionizing irradiation in radiation-resistant and radiation-sensitive mice. Proc Natl Acad Sci USA. 94(14):7572–7576.
  • Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. 2007. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food and chemical toxicology: an international journal published for the British Industrial. Biol Res Assoc. 45(11):2179–2205.
  • Hollman PCH, van Trijp JMP, Buysman MNCP, V.D. Gaag MS, Mengelers MJB, de Vries JHM, Katan MB. 1997. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett. 418(1–2):152–156.
  • Hwang JJ, Lin GL, Sheu SC, Lin FJ. 1999. Effect of ionizing radiation on liver mitochondrial respiratory functions in mice. Chin Med J. 112(4):340–344.
  • Jang JY, Kang MY, Lim YK, Kim JH, Kim JK. 2017. Effects of quercetin on ionizing radiation-induced cellular responses in HepG2 cells. Int J Radiat Res. 15(3):229–239.
  • Jnawali HN, Lee E, Jeong KW, Shin A, Heo YS, Kim Y. 2014. Anti-inflammatory activity of rhamnetin and a model of its binding to c-Jun NH2-terminal kinase 1 and p38 MAPK. J Nat Prod. 77(2):258–263.
  • Kam WW, Banati RB. 2013. Effects of ionizing radiation on mitochondria. Free Rad Biol Med. 65:607–619.
  • Kang J, Kim E, Kim W, Seong KM, Youn H, Kim JW, Kim J, Youn B. 2013. Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines. J Biol Chem. 288(38):27343–27357.
  • Kerimi A, Williamson G. 2018. Differential impact of flavonoids on redox modulation, bioenergetics, and cell signaling in normal and tumor cells: a comprehensive review. Antioxidants Redox Signal. 29:1633–1659.
  • Kim MJ, Jeon D, Kwak C, Ryoo S, Kim Y. 2016. Rhamnetin exhibits anti-tuberculosis activity and protects against lung inflammation. Bull Korean Chem Soc. 37(10):1703–1709.
  • Kocyigit A, Guler EM, Dikilitas M. 2018. Role of antioxidant phytochemicals in prevention, formation and treatment of cancer. Reactive Oxygen Species (ROS) in Living Cells.
  • Korkina LG, Afanas'ev IB. 1997. Antioxidant and chelating properties of flavonoids. Adv Pharmacol. 38:151–163.
  • Kozłowska A, Szostak-Węgierek D. 2017. Flavonoids – food sources, health benefits, and mechanisms involved. In: Mérillon J-M, Ramawat KG, editors. Bioactive molecules in food. Cham: Springer International Publishing; p. 1–27.
  • Kumar S, Pandey AK. 2013. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013:1.
  • Kwon B-E, Song J-H, Song H-H, Kang JW, Hwang SN, Rhee K-J, Shim A, Hong E-H, Kim Y-J, Jeon S-M, et al. 2016. Antiviral activity of oroxylin A against coxsackievirus B3 alleviates virus-induced acute pancreatic damage in mice. PloS One. 11(5):e0155784.
  • Lagerweij T, Hiddingh L, Biesmans D, Crommentuijn MH, Cloos J, Li XN, Kogiso M, Tannous BA, Vandertop WP, Noske DP, et al. 2016. A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer. Oncotarget. 7(24):35776–35788.
  • Landauer MR, Srinivasan V, Seed TM. 2003. Genistein treatment protects mice from ionizing radiation injury. J Appl Toxicol. 23(6):379–385.
  • Larson AJ, Symons JD, Jalili T. 2012. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr. 3(1):39–46.
  • Leach JK, Van Tuyle G, Lin PS, Schmidt-Ullrich R, Mikkelsen RB. 2001. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res. 61(10):3894–3901.
  • Lee M, Son M, Ryu E, Shin YS, Kim JG, Kang BW, Cho H, Kang H. 2015. Quercetin-induced apoptosis prevents EBV infection. Oncotarget. 6(14):12603–12624.
  • Lee S, Shin SY, Lee Y, Park Y, Kim BG, Ahn JH, Chong Y, Lee YH, Lim Y. 2011. Rhamnetin production based on the rational design of the poplar O-methyltransferase enzyme and its biological activities. Bioorg Med Chem Lett. 21(13):3866–3870.
  • Legette LL, Lee WH, Martin BR, Story JA, Arabshahi A, Barnes S, Weaver CM. 2011. Genistein, a phytoestrogen, improves total cholesterol, and synergy, a prebiotic, improves calcium utilization, but there were no synergistic effects. Menopause. 18(8):923–931.
  • Li HB, Chen F. 2005. Isolation and purification of baicalein, wogonin and oroxylin A from the medicinal plant Scutellaria baicalensis by high-speed counter-current chromatography. J Chromatogr A. 1074(1–2):107–110.
  • Li HN, Nie FF, Liu W, Dai QS, Lu N, Qi Q, Li ZY, You QD, Guo QL. 2009. Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. Toxicology. 257(1–2):80–85.
  • Li N, Yu L, Wang J, Gao X, Chen Y, Pan W, Tang B. 2018. A mitochondria-targeted nanoradiosensitizer activating reactive oxygen species burst for enhanced radiation therapy. Chem Sci. 9(12):3159–3164.
  • Li Y, Kucuk O, Hussain M, Abrams J, Cher ML, Sarkar FH. 2006. Antitumor and antimetastatic activities of docetaxel are enhanced by genistein through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/MMP-9 signaling in prostate cancer. Cancer Res. 66(9):4816–4825.
  • Liggins J, Bluck LJ, Runswick S, Atkinson C, Coward WA, Bingham SA. 2000. Daidzein and genistein contents of vegetables. Br J Nutr. 84(5):717–725.
  • Lim R, Morwood CJ, Barker G, Lappas M. 2014. Effect of silibinin in reducing inflammatory pathways in in vitro and in vivo models of infection-induced preterm birth. PloS One. 9(3):e92505.
  • Lin C, Yu Y, Zhao HG, Yang A, Yan H, Cui Y. 2012. Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo. Radiother Oncol. 104(3):395–400.
  • Lin Y, Shi R, Wang X, Shen HM. 2008. Luteolin, a flavonoid with potential for cancer prevention and therapy. CCDT. 8(7):634–646.
  • Liu X, Li P, Hirayama R, Niu Y, Liu X, Chen W, Jin X, Zhang P, Ye F, Zhao T, et al. 2018. Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways. Radiother Oncol. 129(1):84–94.
  • Liu X, Sun C, Jin X, Li P, Ye F, Zhao T, Gong L, Li Q. 2013. Genistein enhances the radiosensitivity of breast cancer cells via G(2)/M cell cycle arrest and apoptosis. Molecules. 18(11):13200–13217.
  • Liu X, Sun C, Liu B, Jin X, Li P, Zheng X, Zhao T, Li F, Li Q. 2016. Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region. Oncotarget. 7(19):27267–27279.
  • Lomax ME, Folkes LK, O'Neill P. 2013. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol. 25(10):578–585.
  • Lu QY, Zhang L, Moro A, Chen MC, Harris DM, Eibl G, Go VL. 2012. Detection of baicalin metabolites baicalein and oroxylin-a in mouse pancreas and pancreatic xenografts. Pancreas. 41(4):571–576.
  • Malik A, Sultana M, Qazi A, Qazi MH, Parveen G, Waquar S, Ashraf AB, Rasool M. 2016. Role of natural radiosensitizers and cancer cell radioresistance: an update. Anal Cell Pathol. 2016:1.
  • Mattarei A, Biasutto L, Rastrelli F, Garbisa S, Marotta E, Zoratti M, Paradisi C. 2010. Regioselective O-derivatization of quercetin via ester intermediates. An improved synthesis of rhamnetin and development of a new mitochondriotropic derivative. Molecules. 15(7):4722–4736.
  • Medhat AM, Azab KS, Said MM, El Fatih NM, El Bakary NM. 2017. Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice. Tumour Biol. 39(10):101042831772848.
  • Meyer H, Bolarinwa A, Wolfram G, Linseisen J. 2006. Bioavailability of apigenin from apiin-rich parsley in humans. Ann Nutr Metab. 50(3):167–172.
  • Miean KH, Mohamed S. 2001. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem. 49(6):3106–3112.
  • Mishra KP. 2004. Cell membrane oxidative damage induced by gamma-radiation and apoptotic sensitivity. J Env Path Tox Oncol. 23(1):61–66.
  • Mitchell JB, Russo A, Cook JA, Straus KL, Glatstein E. 1989. Radiobiology and clinical application of halogenated pyrimidine radiosensitizers. Int J Radiat Biol. 56(5):827–836.
  • Montani C, Penza M, Jeremic M, Biasiotto G, La Sala G, De Felici M, Ciana P, Maggi A, Di Lorenzo D. 2008. Genistein is an efficient estrogen in the whole-body throughout mouse development. Toxicol Sci. 103(1):57–67.
  • Mustafa EH, Abu Zarga M, Abdalla S. 1992. Effects of cirsiliol, a flavone isolated from Achillea fragrantissima, on rat isolated ileum. Gen Pharmacol. 23(3):555–560.
  • Nambiar DK, Rajamani P, Deep G, Jain AK, Agarwal R, Singh RP. 2015a. Silibinin preferentially radiosensitizes prostate cancer by inhibiting DNA repair signaling. Mol Cancer Therapeut. 14(12):2722–2734.
  • Nambiar DK, Rajamani P, Singh RP. 2015b. Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells. Biochem Biophys Res Commun. 456(1):262–268.
  • National Toxicology. 2008. Toxicology and carcinogenesis studies of genistein (Cas No. 446-72-0) in Sprague-Dawley rats (feed study). Natl Toxicol Program Technical Rep Ser. 545:1–240.
  • Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff AI. 2007. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol. 179(10):7121–7127.
  • Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. 2001. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 74(4):418–425.
  • Noda N, Wakasugi H. 2001. Cancer and oxidative stress. Jpn Med Assoc J. 44(12):535.
  • Perez-Vizcaino F, Duarte J, Andriantsitohaina R. 2006. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Rad Res. 40(10):1054–1065.
  • Pietta PG. 2000. Flavonoids as antioxidants. J Nat Prod. 63(7):1035–1042.
  • Puthli A, Tiwari R, Mishra KP. 2013. Biochanin A enhances the radiotoxicity in colon tumor cells. J Environ Pathol Toxicol Oncol. 32(3):189–203.
  • Rathee P, Chaudhary H, Rathee S, Rathee D, Kumar V, Kohli K. 2009. Mechanism of action of flavonoids as anti-inflammatory agents: a review. IADT. 8(3):229–235.
  • Rithidech KN, Tungjai M, Reungpatthanaphong P, Honikel L, Simon SR. 2012. Attenuation of oxidative damage and inflammatory responses by apigenin given to mice after irradiation. Mutat Res. 749(1–2):29–38.
  • Rithidech KN, Tungjai M, Whorton EB. 2005. Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes. Mutat Res. 585(1–2):96–104.
  • Rockwell S, Dobrucki IT, Kim EY, Marrison ST, Vu VT. 2009. Hypoxia and radiation therapy: past history, ongoing research, and future promise. CMM. 9(4):442–458.
  • Ross JA, Kasum CM. 2002. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 22(1):19–34.
  • Sak K. 2014. Cytotoxicity of dietary flavonoids on different human cancer types. Phcog Rev. 8(16):122–146.
  • Sandhya T, Mishra KP. 2006. Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants. Cancer Lett. 238(2):304–313.
  • Saul RC. 2017. Flavonoids: important biocompounds in food. In: Saraí CH, editor. Flavonoids. Rijeka: IntechOpen; p. 16.
  • Schmidt-Ullrich RK. 2003. Molecular targets in radiation oncology. Oncogene. 22(37):5730–5733.
  • Seiwert TY, Salama JK, Vokes EE. 2007. The concurrent chemoradiation paradigm–general principles. Nat Rev Clin Oncol. 4(2):86–100.
  • Shah RC, Mehta CR, Wheeler TS. 1936.The constitution of oroxylin-A, a yellow colouring matter from the root-bark of Oroxylum indicum, vent. J Chem Soc). 131:591–593.
  • Shenoy MA, Asquith JC, Adams GE, Michael BD, Watts ME. 1975. Time-resolved oxygen effects in irradiated bacteria and mammalian cells: a rapid-mix study. Radiat Res. 62(3):498–512.
  • Shimoi K, Masuda S, Furugori M, Esaki S, Kinae N. 1994. Radioprotective effect of antioxidative flavonoids in gamma-ray irradiated mice. Carcinogenesis. 15(11):2669–2672.
  • Shimoi K, Masuda S, Shen B, Furugori M, Kinae N. 1996. Radioprotective effects of antioxidative plant flavonoids in mice. Mutat Res. 350(1):153–161.
  • Shukla S, Gupta S. 2010. Apigenin: a promising molecule for cancer prevention. Pharm Res. 27(6):962–978.
  • Singh P, Mishra SK, Noel S, Sharma S, Rath SK. 2012. Acute exposure of apigenin induces hepatotoxicity in Swiss mice. PloS One. 7(2):e31964.
  • Son TG, Gong EJ, Bae MJ, Kim SD, Heo K, Moon C, Yang K, Kim JS. 2013. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice. BMC Complement Altern Med. 13(1):103–103.
  • Spalding AC, Lawrence TS. 2006. New and emerging radiosensitizers and radioprotectors. Cancer Invest. 24(4):444–456.
  • Sudhakaran M, Sardesai S, Doseff AI. 2019. Flavonoids: new frontier for immuno-regulation and breast cancer control. Antioxidants. 8(4):103.
  • Surai PF. 2015. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants. 4(1):204–247.
  • Swati G, Ahmed M, Mishra K. 2009. Enhancement of gamma radiation-induced cytotoxicity of breast cancer cells by curcumin. Mol Cell Pharmacol. 1:208–217.
  • Tan C, Qian X, Ge Y, Yang B, Wang F, Guan Z, Cai J. 2016. Oroxylin a could be a Promising Radiosensitizer for Esophageal Squamous Cell Carcinoma by Inducing G2/M Arrest and Activating Apoptosis. Pathol Oncol Res. 23:323–328.
  • Taneja N, Tjalkens R, Philbert MA, Rehemtulla A. 2001. Irradiation of mitochondria initiates apoptosis in a cell free system. Oncogene. 20(2):167–177.
  • Tang Q, Ma J, Sun J, Yang L, Yang F, Zhang W, Li R, Wang L, Wang Y, Wang H. 2018. Genistein and AG1024 synergistically increase the radiosensitivity of prostate cancer cells. Oncol Rep. 40(2):579–588.
  • Theoharides TC, Asadi S, Panagiotidou S. 2012. A case series of a luteolin formulation (NeuroProtek(R)) in children with autism spectrum disorders. Int J Immunopathol Pharmacol. 25(2):317–323.
  • Tiwari P, Kumar A, Ali M, Mishra KP. 2010. Radioprotection of plasmid and cellular DNA and Swiss mice by silibinin. Mutat Res. 695(1–2):55–60.
  • Tiwari P, Kumar A, Balakrishnan S, Kushwaha HS, Mishra KP. 2009. Radiation-induced micronucleus formation and DNA damage in human lymphocytes and their prevention by antioxidant thiols. Mutat Res. 676(1–2):62–68.
  • Tiwari P, Kumar A, Balakrishnan S, Kushwaha HS, Mishra KP. 2011. Silibinin-induced apoptosis in MCF7 and T47D human breast carcinoma cells involves caspase-8 activation and mitochondrial pathway. Cancer Invest. 29(1):12–20.
  • Tiwari P, Mishra KP. 2015. Silibinin in cancer therapy: a promising prospect. Cancer Res Front. 1(3):303–318.
  • Tiwari P, Mishra KP. 2017. Role of flavonoids in DNA damage and carcinogenesis prevention. J Carcinog Mutagen. 8(4):297.
  • Tsilioni I, Taliou A, Francis K, Theoharides TC. 2015. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry. 5:e647.
  • Ueda H, Yamazaki C, Yamazaki M. 2002. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol Pharm Bull. 25(9):1197–1202.
  • van Rijn J, van den Berg J. 1997. Flavonoids as enhancers of x-ray-induced cell damage in hepatoma cells. Clin Cancer Res. 3(10):1775–1779.
  • Vessal M, Hemmati M, Vasei M. 2003. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol Toxicol Pharmacol. 135C(3):357–364.
  • Wang H, Mu X, He H, Zhang X-D. 2018. Cancer radiosensitizers. Trends Pharmacol Sci. 39(1):24–48.
  • Wardman P. 2007. Chemical radiosensitizers for use in radiotherapy. Clin Oncol. 19(6):397–417.
  • Watanabe N, Hirayama R, Kubota N. 2007. The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids. JRR. 48(1):45–50.
  • Yang Z, Kulkarni K, Zhu W, Hu M. 2012. Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME. ACAMC. 12(10):1264–1280.
  • Yarnold J. 1997. Molecular aspects of cellular responses to radiotherapy. Radiother Oncol. 44(1):1–7.
  • Yashar CM, Spanos WJ, Taylor DD, Gercel-Taylor C. 2005. Potentiation of the radiation effect with genistein in cervical cancer cells. Gynecol Oncol. 99(1):199–205.
  • Yasuda MT, Fujita K, Hosoya T, Imai S, Shimoi K. 2015. Absorption and metabolism of luteolin and its glycosides from the Extract of Chrysanthemum morifolium flowers in rats and Caco-2 cells. J Agric Food Chem. 63(35):7693–7699.
  • Ye M, Wang Q, Zhang W, Li Z, Wang Y, Hu R. 2014. Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2/ARE activation. Biochem Cell Biol. 92(5):337–348.
  • Zhang Z, Jin F, Lian X, Li M, Wang G, Lan B, He H, Liu G-D, Wu Y, Sun G, et al. 2018. Genistein promotes ionizing radiation-induced cell death by reducing cytoplasmic Bcl-xL levels in non-small cell lung cancer. Sci Rep. 8(1):328.
  • Zhou DG, Diao BZ, Zhou W, Feng JL. 2016. Oroxylin A inhibits allergic airway inflammation in ovalbumin (OVA)-induced asthma murine model. Inflammation. 39(2):867–872.
  • Zou Z, Chang H, Li H, Wang S. 2017. Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis. 22(11):1321–1335.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.